Revisiting the Electrochemical Impedance Spectroscopy of Porous Electrodes in Li-ion Batteries by Employing Reference Electrode.

Electrochemical impedance spectroscopy (EIS), characterized by its non-destructive and in-situ nature, plays a crucial role in comprehending the thermodynamic and kinetic processes occurring with Li-ion batteries. However, there is a lack of consistent and coherent physical interpretations for the EIS of porous electrodes. Therefore, it is imperative to conduct thorough investigations into the underlying physical mechanisms of EIS. Herein, by employing reference electrode in batteries, we revisit the associated physical interpretation of EIS at different frequency. Combining different battery configurations, temperature-dependent experiments, and elaborated distribution of relaxation time analysis, we find that the ion transport in porous electrode channels and pseudo-capacitance behavior dominate the high-frequency and mid-frequency impedance arcs, respectively. This work offers a perspective for the physical interpretation of EIS and also sheds light on the understanding of EIS characteristics in other advanced energy storage systems.

In(OTf)3-catalyzed formal (4 + 3) cycloaddition reactions of 3-benzylideneindoline-2-thiones with 2-indolylmethanols.

We report the In(OTf)3-catalyzed formal (4 + 3) cycloaddition of 3-benzylideneindoline-2-thiones with 2-indolylmethanols. This reaction not only broadens the synthetic utility of 3-benzylideneindoline-2-thiones as scarce indole-based sulfur-containing four-atom building blocks, but also provides a rapid and facile access to synthesize diindole-annulated tetrahydrothiepines.

Familiarity of evidence based practices in Chinese caregivers of autistic children.

Although researchers have investigated special educators' and clinicians' knowledge and use of evidence-based practices (EBPs), there is very little research on caregivers' perception of the importance of EBPs for their autistic children. Moreover, there is even less research on how EBPs have been translated or disseminated in international communities not within the English-speaking, Western population. In order to provide appropriate support for caregivers of autistic children in all communities, we need more information to identify possible barriers that may affect caregiver involvement. We used a survey to ask 81 Chinese caregivers of autistic children in Guangzhou, China to investigate their familiarity with EBPs for autistic individuals and any external sources used inform their decision about treatment options for their autistic child. Results showed that 58.6% of the participants had no knowledge of what an EBP was and an additional 29.7% of the participants had heard of EBPs but not sure what they were. These results amplify the need for increased dispersion of ASD intervention knowledge to global communities and how to increase caregiver knowledge on treatment options for their autistic child.

Phytochemicals targeting ferroptosis in cardiovascular diseases: Recent advances and therapeutic perspectives.

Ferroptosis is a form of iron-dependent regulatory cell death that is related to the pathogenesis and progression of various cardiovascular diseases, such as arrhythmia, diabetic cardiomyopathy, myocardial infarction, myocardial ischemia/reperfusion injury, and heart failure. This makes it a promising therapeutic target for cardiovascular diseases. It is interesting that a significant number of cardiovascular disease treatment drugs derived from phytochemicals have been shown to target ferroptosis, thus producing cardioprotective effects. This study offers a concise overview of the initiation and control mechanisms of ferroptosis. It discusses the core regulatory factors of ferroptosis as potential new therapeutic targets for various cardiovascular diseases, elucidating how ferroptosis influences the progression of cardiovascular diseases. In addition, this review systematically summarizes the regulatory effects of phytochemicals on ferroptosis, emphasizing their potential mechanisms and clinical applications in treating cardiovascular diseases. This study provides a reference for further elucidating the molecular mechanisms of phytochemicals in treating cardiovascular diseases. This may accelerate their application in the treatment of cardiovascular diseases and is worth further research in this field.

A Least-Square Unified Framework for Spatial Filtering in SSVEP-based BCIs.

The steady-state visual evoked potential (SSVEP) has become one of the most prominent BCI paradigms with high information transfer rate, and has been widely applied in rehabilitation and assistive applications. This paper proposes a least-square (LS) unified framework to summarize the correlation analysis (CA)-based SSVEP spatial filtering methods from a machine learning perspective. Within this framework, the commonalities and differences between various spatial filtering methods appear apparent, the interpretation of computational factors becomes intuitive, and spatial filters can be determined by solving a generalized optimization problem with non-linear and regularization items. Moreover, the proposed LS framework provides the foundation of utilizing the knowledge behind these spatial filtering methods in further classification/regression model designs. Through a comparative analysis of existing representative spatial filtering methods, recommendations are made for the superior and robust design strategies. These recommended strategies are further integrated to fill the research gaps and demonstrate the ability of the proposed LS framework to promote algorithmic improvements, resulting in five new spatial filtering methods. This study could offer significant insights in understanding the relationships between various design strategies in the spatial filtering methods from the machine learning perspective, and would also contribute to the development of the SSVEP recognition methods with high performance.

Two-dimensional Perovskitoids Enhance Stability in Perovskite Solar Cells.

Two-dimensional (2D)/three-dimensional (3D) perovskite heterostructures have played a key role in advancing the performance of perovskite solar cells (PSCs)1,2. However, the migration of cations between 2D and 3D layers results in the disruption of octahedral networks that leads to degradation in performance over time3,4. We hypothesized that perovskitoids, with robust organic-inorganic networks enabled by edge- and face-sharing, could impede ion migration. We explored a set of perovskitoids of varying dimensionality, and found that cation migration within perovskitoid/perovskite heterostructures was suppressed compared to the 2D/3D perovskite case. Increasing the dimensionality of perovskitoids improves charge transport when they are interfaced with 3D perovskite surfaces - this the result of enhanced octahedral connectivity and out-of-plane orientation. The 2D perovskitoid (A6BfP)8Pb7I22 (A6BfP: N-aminohexyl-benz[f]-phthalimide) provides efficient passivation of perovskite surfaces and enables uniform large-area perovskite films. Devices based on perovskitoid/perovskite heterostructures achieve a certified quasi-steady-state power conversion efficiency of 24.6% for centimeter-area PSCs. We removed the fragile hole transport layers and showed stable operation of the underlying perovskitoid/perovskite heterostructure at 85°C for 1,250 hours for encapsulated large-area devices in an air ambient.

FOXN2, identified as a novel biomarker in serum, modulates the transforming growth factor-beta signaling pathway through its interaction with partitioning defective 6 homolog alpha, contributing to the pathogenesis of gastric cancer.

BACKGROUND AND OBJECTIVE: Dysregulated expression of Forkhead Box N2 (FOXN2) has been detected in various cancer types. However, the underlying mechanisms by which FOXN2 contributes to the onset and progression of gastric cancer (GC) remain largely unexplored. This study aimed to elucidate the potential role of FOXN2 within GC, its downstream molecular mechanisms, and its feasibility as a novel serum biomarker for GC. METHODS: Tissue samples from GC patients and corresponding non-cancerous tissues were collected. Peripheral blood samples were obtained from GC patients and healthy controls. The expression of FOXN2 was determined using quantitative real-time PCR, western blotting, and immunohistochemistry. The expression of FOXN2 in GC cells was modulated by transfection with small interfering RNA (siRNA) or the pcDNA 3.1 expression vector. Cell proliferation was assessed using the Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine incorporation assays. The migratory and invasive capacities of cells were evaluated by Transwell assays, apoptosis rates were measured by flow cytometry, and the expression of proliferative, apoptotic, and epithelial-mesenchymal transition (EMT) markers were assessed by western blot analysis. RESULTS: FOXN2 was found to be overexpressed in the serum, tissues, and cells of GC, correlating with distant metastasis and TNM staging. FOXN2 demonstrated diagnostic value in differentiating GC patients from healthy individuals, with higher levels of FOXN2 being indicative of poorer survival rates. Silencing FOXN2 in vitro inhibited the proliferation, invasion, migration, and EMT of GC cells, while promoting apoptosis. FOXN2 was shown to regulate the transforming growth factor-beta (TGFß) receptor signaling pathway in GC cells via its interaction with Partitioning Defective 6 Homolog Alpha (PARD6A). CONCLUSION: In summary, our data suggest that FOXN2 acts as an oncogenic factor in GC, modulating the TGFß pathway by binding to PARD6A, thereby influencing gastric carcinogenesis. This study underscores the functional significance of FOXN2 as a potential serum biomarker and therapeutic target in GC.

Association between Pre-operative Body Mass Index and Surgical Infection in Perihilar Cholangiocarcinoma Patients Treated with Curative Resection: A Multi-center Study.

Background: The objective of this study was to investigate the association between pre-operative body mass index (BMI) and surgical infection in perihilar cholangiocarcinoma (pCCA) patients treated with curative resection. Methods: Consecutive pCCA patients were enrolled from four tertiary hospitals between 2008 and 2022. According to pre-operative BMI, the patients were divided into three groups: low BMI (≤18.4 kg/m2), normal BMI (18.5-24.9 kg/m2), and high BMI (≥25.0 kg/m2). The incidence of surgical infection among the three groups was compared. Multivariable logistic regression models were used to determine the independent risk factors associated with surgical infection. Results: A total of 371 patients were enrolled, including 283 patients (76.3%) in the normal BMI group, 30 patients (8.1%) in the low BMI group, and 58 patients (15.6%) in the high BMI group. The incidence of surgical infection was significantly higher in the patients in the low BMI and high BMI groups than in the normal BMI group. The multivariable logistic regression model showed that low BMI and high BMI were independently associated with the occurrence of surgical infection. Conclusions: The pCCA patients with a normal BMI treated with curative resection could have a lower risk of surgical infection than pCCA patients with an abnormal BMI.

The Influence of Visceral Adiposity on Overall Survival: Exploring "Obesity Paradox" Among Hepatocellular Carcinoma Patients Who Receiving Immunotherapy.

Purpose: The impact of visceral adiposity on overall survival (OS) in hepatocellular carcinoma (HCC) receiving immunotherapy was unclear. We aimed to determine how visceral adiposity affected OS and explore the interrelationships between visceral adiposity, body mass index (BMI), and other body compositions. Patients and Methods: Data from three centers were retrospectively analyzed. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI) were used to define each body composition. The BMI subgroups included the underweight, the normal weight, and the obesity. The Log rank test compared survival curves calculated by the Kaplan-Meier method. The relationships between body compositions and BMI with OS were examined using Cox proportional risk regression models. Results: A total of 305 patients who met the criteria were included. Patients with low VATI had significantly worse OS (P = 0.001). The protections of VATI (P = 0.011) on OS were independent of covariates. However, after additional adjustment of SMI, the effect of VATI on OS disappeared (P = 0.146), but the effect of SMD on OS did not (P = 0.021). BMI has a significant U-shaped relationship with OS, and the effect of BMI on OS equally disappeared after additional adjustment by SMI. Conclusion: This study first demonstrated that high VATI and mid-level BMI were protective for the survival of patients with HCC receiving immunotherapy. Skeletal muscle status (including SMI and SMD) may be the better predictor for outcomes of patients with HCC receiving immunotherapy.

Assessing the merits: an opinion on the effectiveness of simulation techniques in tumor subclonal reconstruction.

Summary: Neoplastic tumors originate from a single cell, and their evolution can be traced through lineages characterized by mutations, copy number alterations, and structural variants. These lineages are reconstructed and mapped onto evolutionary trees with algorithmic approaches. However, without ground truth benchmark sets, the validity of an algorithm remains uncertain, limiting potential clinical applicability. With a growing number of algorithms available, there is urgent need for standardized benchmark sets to evaluate their merits. Benchmark sets rely on in silico simulations of tumor sequence, but there are no accepted standards for simulation tools, presenting a major obstacle to progress in this field. Availability and implementation: All analysis done in the paper was based on publicly available data from the publication of each accessed tool.

Membranous nephropathy: pathogenesis and treatments.

Membranous nephropathy (MN), an autoimmune disease, can manifest at any age and is among the most common causes of nephrotic syndrome in adults. In 80% of cases, the specific etiology of MN remains unknown, while the remaining cases are linked to drug use or underlying conditions like systemic lupus erythematosus, hepatitis B virus, or malignancy. Although about one-third of patients may achieve spontaneous complete or partial remission with conservative management, another third face an elevated risk of disease progression, potentially leading to end-stage renal disease within 10 years. The identification of phospholipase A2 receptor as the primary target antigen in MN has brought about a significant shift in disease management and monitoring. This review explores recent advancements in the pathophysiology of MN, encompassing pathogenesis, clinical presentations, diagnostic criteria, treatment options, and prognosis, with a focus on emerging developments in pathogenesis and therapeutic strategies aimed at halting disease progression. By synthesizing the latest research findings and clinical insights, this review seeks to contribute to the ongoing efforts to enhance our understanding and management of this challenging autoimmune disorder.

[Advances in Nanotechnology-Based Drug Delivery Systems in the Treatment of Hepatocellular Carcinoma].

Primary liver cancer is one of the most common malignant tumors of the digestive system,of which hepatocellular carcinoma (HCC) accounts for more than 90% of the total cases.The patients with early HCC treated by surgical resection generally demonstrate good prognosis.However,due to the insidious onset,HCC in the vast majority of patients has progressed to the mid-to-late stage when being diagnosed.As a result,surgical treatment has unsatisfactory effects,and non-surgical treatment methods generally have severe side effects and low tumor selectivity.Nanoparticles (NP) with small sizes,large specific surface areas,and unique physical and chemical properties have become potential carriers for the delivery of therapeutic agents such as drugs,genes,and cytokines.The nano-delivery systems with NP as the carrier can regulate the metabolism and transformation of drugs,genes,and cytokines in vivo from time,space,and dose via functional modification,showing great potential in the treatment of HCC.This paper introduces the current status and advantages of several common nano-delivery systems,including organic nano-carriers,inorganic nano-carriers,and exosomes,in the treatment of HCC.Furthermore,this paper summarizes the mechanisms of NP-based nano-carriers in treating HCC and provides reference for the development of new nano-delivery systems.

Quantitative Assessment of Acute Intracranial Clot and Collaterals on High Resolution Magnetic Resonance Imaging.

INTRODUCTION: There has been an increasing demand for imaging methods that provide a comprehensive evaluation of intracranial clot and collateral circulation, which are helpful for clinical decision-making and predicting functional outcomes. We aimed to quantitatively evaluate acute intracranial clot burden and collaterals on high-resolution magnetic resonance imaging (HR-MRI). METHODS: We analyzed acute ischemic stroke patients with internal carotid artery or middle cerebral artery occlusion in a prospective multicenter study. The clot burden was scored on a scale of 0-10 based on the clot location on HR-MRI. The collateral score was assigned on a scale of 0-3 using the minimum intensity projection from HR-MRI. Uni- and multivariable logistic regression analyses were performed to assess their correlation with clinical outcome (modified Rankin Scale >2 at 90 days). Thresholds were defined to dichotomize into low and high score groups and predictive performances were assessed for clinical and radiologic outcomes. RESULTS: Ninety-nine patients (mean age of 60.77 ± 11.54 years) were included in the analysis. The interobserver correlation was 0.89 (95% CI: 0.77-0.95) for the clot burden score and 0.78 (95% CI: 0.53-0.90) for the collateral score. Multivariable logistic regression analysis demonstrated that the collateral score (odds ratio: 0.41, 95% CI: 0.19-0.90) was significantly associated with clinical outcomes. A better functional outcome was observed in the group with clot burden scores greater than 7 (p=0.011). A smaller final infarct size and a higher diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score were observed in the group with collateral scores greater than 1 (all p<0.05). CONCLUSIONS: HR-MRI offers a new tool for quantitative assessment of clot burden and collaterals simultaneously in future clinical practices and research endeavors.

Hepatic arterial infusion chemotherapy plus camrelizumab and apatinib for advanced hepatocellular carcinoma.

BACKGROUND AND AIMS: There is limited information on combination of hepatic arterial infusion chemotherapy (HAIC) and systemic therapy for advanced hepatocellular carcinoma (Ad-HCC). We aim to compare the efficacy and safety of HAIC plus camrelizumab (a PD-1 inhibitor) and apatinib (an VEGFR-2 inhibitor) versus camrelizumab and apatinib for Ad-HCC. METHODS: From April 2019 to October 2022, 416 patients with Ad-HCC who received either HAIC plus camrelizumab and apatinib (TRIPLET protocol, n = 207) or camrelizumab and apatinib (C-A protocol, n = 209) were reviewed retrospectively. The propensity score matching (PSM) was used to reduce selective bias. Overall survival (OS) and progression-free survival (PFS) were compared using the Kaplan-Meier method with the log-rank test. Cox regression analyses of independent prognostic factors were evaluated. RESULTS: After PSM 1:1, 109 patients were assigned to two groups. The median OS of not reached in the TRIPLET group was significantly longer than that of 19.9 months in the C-A group (p < 0.001), while in the TRIPLET group, the median PFS of 11.5 months was significantly longer than that of 9.6 months in the C-A group (p < 0.001). Multivariate analyses showed that the factors significantly affected the OS were CTP grade, tumor number > 3, and TRIPLET treatment (p < 0.001). Grade 3/4 adverse events occurred at a rate of 82.1% vs. 71.3% in TRIPLET and C-A groups, respectively. CONCLUSION: The TRIPLET protocol has promising survival benefits in the management of patients with Ad-HCC, with acceptable safety. TRAIL REGISTRATION: The study has been retrospectively registered at Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ , ChiCTR2300075828).

The impact of Astragaloside IV on the inflammatory response and gut microbiota in cases of acute lung injury is examined through the utilization of the PI3K/AKT/mTOR pathway.

OBJECTIVES: Astragaloside IV (AS-IV) is a natural triterpenoid saponin compound with a variety of pharmacological effects, and several studies have clarified its anti-inflammatory effects, which may make it an effective alternative treatment against inflammation. In the study, we aimed to investigate whether AS-IV could attenuate the inflammatory response to acute lung injury and its mechanisms. METHODS: Different doses of AS-IV (20mg·kg-1, 40mg·kg-1, and 80mg·kg-1) were administered to the ALI rat model, followed by collection of serum and broncho alveolar lavage fluid (BALF) for examination of the inflammatory response, and HE staining of the lung and colon tissues, and interpretation of the potential molecular mechanisms by quantitative real-time PCR (qRT-PCR), Western blotting (WB). In addition, fecal samples from ALI rats were collected and analyzed by 16S rRNA sequencing. RESULTS: AS-IV decreased the levels of TNF-α, IL-6, and IL-1ß in serum and BALF of mice with Acute lung injury (ALI). Lung and colon histopathology confirmed that AS-IV alleviated inflammatory infiltration, tissue edema, and structural changes. qRT-PCR and WB showed that AS-IV mainly improved inflammation by inhibiting the expression of PI3K, AKT and mTOR mRNA, and improved the disorder of intestinal microflora by increasing the number of beneficial bacteria and reducing the number of harmful bacteria. CONCLUSION: AS-IV reduces the expression of inflammatory factors by inhibiting the PI3K/AKT/mTOR pathway and optimizes the composition of the gut microflora in AIL rats.

Phage display-derived alpaca nanobodies as potential therapeutics for Naja atra snake envenomation.

Naja atra, the Chinese cobra, is a major cause of snake envenomation in Asia, causing hundreds of thousands of clinical incidents annually. The current treatment, horse serum-derived antivenom, has unpredictable side effects and presents manufacturing challenges. This study focused on developing new-generation snake venom antidotes by using microbial phage display technology to derive nanobodies from an alpaca immunized with attenuated N. atra venom. Following confirmation of the immune response in the alpaca, we amplified VHH genes from isolated peripheral blood mononuclear cells and constructed a phage display VHH library of 1.0 × 107 transformants. After four rounds of biopanning, the enriched phages exhibited increased binding activity to N. atra venom. Four nanobody clones with high binding affinities were selected: aNAH1, aNAH6, aNAH7, and aNAH9. Specificity testing against venom from various snake species, including two Southeast Asian cobra species, revealed nanobodies specific to the genus Naja. An in vivo mouse venom neutralization assay demonstrated that all nanobodies prolonged mouse survival and aNAH6 protected 66.6% of the mice from the lethal dosage. These findings highlight the potential of phage display-derived nanobodies as valuable antidotes for N. atra venom, laying the groundwork for future applications in snakebite treatment.IMPORTANCEChinese cobra venom bites present a formidable medical challenge, and current serum treatments face unresolved issues. Our research applied microbial phage display technology to obtain a new, effective, and cost-efficient treatment approach. Despite interest among scientists in utilizing this technology to screen alpaca antibodies against toxins, the available literature is limited. This study makes a significant contribution by introducing neutralizing antibodies that are specifically tailored to Chinese cobra venom. We provide a comprehensive and unbiased account of the antibody construction process, accompanied by thorough testing of various nanobodies and an assessment of cross-reactivity with diverse snake venoms. These nanobodies represent a promising avenue for targeted antivenom development that bridges microbiology and biotechnology to address critical health needs.

Engineering of dual recognition functional aptamer-molecularly imprinted polymeric solid-phase microextraction for detecting of 17ß-estradiol in meat samples.

In this study, an enhanced selective recognition strategy was employed to construct a novel solid-phase microextraction fiber coating for the detection of 17ß-estradiol, characterized by the combination of aptamer biorecognition and molecularly imprinted polymer recognition. Benefiting from the combination of molecularly imprinted and aptamer, aptamer-molecularly imprinted (Apt-MIP) fiber coating had synergistic recognition effect. The effects of pH, ion concentration, extraction time, desorption time and desorption solvent on the adsorption capacity of Apt-MIP were investigated. The adsorption of 17ß-estradiol on Apt-MIP followed pseudo-second order kinetic model, and the Freundlich isotherm. The process was exothermic and thermodynamically spontaneous. Compared with polymers that only rely on imprinted recognition, non-imprinted recognition or aptamer affinity, Apt-MIP had the best recognition performance, which was 1.30-2.20 times that of these three materials. Furthermore, the adsorption capacity of Apt-MIP for 17ß-estradiol was 885.36-1487.52 times than that of polyacrylate and polydimethylsiloxane/divinylbenzone commercial fiber coatings. Apt-MIP fiber coating had good stability and could be reused for more than 15 times. Apt-MIP solid-phase microextraction coupled with high-performance liquid chromatography was successfully applied to the determination of 17ß-estradiol in pork, chicken, fish and shrimp samples, with satisfactory recoveries of 79.61 %-105.70 % and low limits of detection (0.03 µg/kg). This work provides new perspectives and strategies for sample pretreatment techniques based on molecular imprinting technology and improves analytical performance.

Effects of Enterobacter cloacae insecticidal protein on the Duox-ROS system and midgut bacterial community and function of Galleria mellonella larvae.

BACKGROUND: Enterobacter cloacae insecticidal proteins have been reported to kill Galleria mellonella larvae through affecting their midgut microbiome. However, the mechanisms involved remain unclear. Here we aim to investigate how the insecticidal proteins act on the midgut Duox-ROS system and microbial community of G. mellonella larvae. METHODS: Reverse transcription qPCR and fluorescence probes were utilized to assess the Duox expression levels and to evaluate quantitative changes of the ROS levels. Sequencing of the 16S rRNA gene sequences of the midgut bacteria of G. mellonella larvae was conducted for further analyses of bacterial diversity, composition, and abundance. RESULTS: After the injection of the insecticidal proteins, the Duox expression levels first increased within 28 h, then dramatically peaked at 36 h, and slowly decreased thereafter. Simultaneously, the ROS levels increased significantly at 36 h, peaked at 48 h, and rapidly declined to the normal level at 60 h. Responsive to the change of the ROS levels, the structure of the midgut microbial community was altered substantially, compared to that of the untreated larvae. The relative abundance of Enterobacteriaceae and other specific pathogenic bacteria increased significantly, whereas that of Lactobacillus decreased sharply. Importantly, notable shifts were observed in the crucial midgut predicted metabolic functions, including membrane transportation, carbohydrate metabolism, and amino acid metabolism. CONCLUSION: Insecticidal proteins of E. cloacae kill G. mellonella larvae mainly through generation of high oxidative stress, alterations of the midgut microbial community and function, and damage to the physiological functions. These findings provide insights into the inhibition mechanism of E. cloacae insecticidal proteins to G. mellonella larvae.